During the past years the candidate thoroughly examined the central nervous system regulation of various gastrointestinal functions by neuropeptides in vivo applying 'classical' physiological techniques. Neuropeptides and peptide hormones are distributed in distinct regions of the brain and the gut subserving distinct biological functions. The factors responsible for their tissue-specific expression as well as their physiologic (endogenous) importance for homeostatic control are unknown. Very recent studies indicated that gene transcription in eukaryotes is controlled by the concerted actions of multiple nuclear binding proteins (transcription factors), that bind to DNA regulatory elements and act to increase the rate of transcriptional initiation. Transcription factors may direct the precise temporal, spatial, and homeostatic patterns of differential gene expression required by complex organisms. It is proposed to clone, isolate, sequence, and functionally characterize new transcription factors from brain and gut using recombinant DNA technology, gel shift, protein-DNA binding, and co-transfection assays. Expression of these endogenous importance determined in mice homozygous for a null transcription strategies. Dr. Rosenfeld's laboratory as part of the Eucaryotic Regulatory Biology Program at UCSD offers unique opportunities to address these issues. The results of these studies, once applied to human biology, may shed new light on the pathophysiology of secretory and motility disorders of the gut, provide important insights into the transcriptional regulation of gene expression itself, and delineate possible mechanisms determining the distinct tissue-specific expression of regulatory peptides in the neuroendocrine system. The candidate will pursue a career as a physician-scientist in Gastroenterology within the Department of Medicine at UCSD. To extend the studies in neuropeptide biology towards a more basic, molecular level and to allow protected, supervised research in a new field, support as provided by the Clinical Investigator Award will be critical to allow the transition from animal physiology to molecular and cellular biology.